CHAPTER 29: Antimicrobial Photodynamic Therapy: New Anti-Infectives in the Age of Resistance

Photodynamic therapy (PDT) was discovered over 100 years ago by observing light-mediated killing of microorganisms in the presence of certain dyes. Throughout the period from 1970 to 2000, cancer was the overwhelmingly most popular target disease in PDT research. Now, with the inexorable rise of multidrug resistance amongst pathogenic microbes, photodynamic inactivation (PDI) has made somewhat of a comeback. Anticancer photosensitizers (PSs) tend to be lipophilic with little or no overall charge, and mostly operate via type II photochemistry. On the other hand, antimicrobial PSs should have pronounced cationic charges (especially for Gram-negative bacteria), and in many cases can carry out type I photochemistry, producing hydroxyl radicals. Microbial cells have been found to be unable to develop resistance to PDI, and multidrug-resistant strains are equally susceptible. In clinical applications, the PSs are usually topically introduced into the infected area and, with a short drug–light interval, show good selectivity for microbial cells over host mammalian cells. The current clinical applications of antimicrobial PDT include localized infections such as periodontitis, sinusitis, nasal decontamination and infected wounds and ulcers. With the continuing unstoppable rise of antibiotic resistance, antimicrobial PDT is expected to grow in importance in the years to come.